The purpose of the project is to collect information about the sensitivity of hyperplastic nodules in the liver of ethionine-fed rats to acute and chronic effects of ethionine. The development of areas of hyperplasia and hyperplastic nodules is regarded as the most important precancerous step in hepatocarcinogenesis and apparently the hyperplastic nodules are resistant to some toxic effects of DL-ethionine. The L-ethionine uptake by hyperplastic nodules was compared with that of the surrounding tissue of the same rat and of the normal liver tissue. It was found that the concentration of L-ethionine and its metabolites was significantly increased in hyperplastic nodules and adjacent liver tissue compared to normal liver. The capability to accumulate S-adenosylethionine in liver of rats ingesting DL-ethionine was decreased; the decreased was systematically higher in the adjacent liver tissue than in hyperplastic nodules. The role of hepatic ATP and of the pattern of S-adenosylmethionine synthetase in these alterations is being investigated.